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Moreover, tumor cells exhibit high expression of CD47 \u201cdon't eat me\u201d signal, which obstructs macrophage phagocytosis. The precise and efficient activation of TAMs is a promising approach to tumor immunotherapy; however, re\u2010education of macrophages remains a challenge. Bacteria\u2010derived outer membrane vesicles (OMVs) are highly immunogenic nanovesicles that can robustly stimulate macrophages. Here, an OMV\u2010based controllable two\u2010way adaptor is reported, in which a CD47 nanobody (CD47nb) is fused onto OMV surface (OMV\u2010CD47nb), with the outer surface coated with a polyethylene glycol (PEG) layer containing diselenide bonds (PEG\/Se) to form PEG\/Se@OMV\u2010CD47nb. The PEG\/Se layer modification not only mitigates the immunogenicity of OMV\u2010CD47nb, thereby remarkedly increasing the dose that can be administered safely through intravenous injection, but also equips the formulation with radiation\u2010triggered controlled release of OMV\u2010CD47nb. Application of radiation to tumors in mice injected with the nanoformulation results in remodeling of TME. As two\u2010way adaptors, OMV\u2010CD47nb activates TAM phagocytosis of tumor cells via multiple pathways, including induction of M1 polarization and blockade of \u201cdon't eat me\u201d signal. Moreover, this activation of TAMs results in the stimulation of T cell\u2010mediated antitumor immunity through effective antigen presentation.<\/jats:p>","DOI":"10.1002\/adma.202206200","type":"journal-article","created":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T20:38:10Z","timestamp":1660941490000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":208,"title":["Engineered Bacterial Outer Membrane Vesicles as Controllable Two\u2010Way Adaptors to Activate Macrophage Phagocytosis for Improved Tumor Immunotherapy"],"prefix":"10.1002","volume":"34","author":[{"given":"Qingqing","family":"Feng","sequence":"first","affiliation":[{"name":"CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety &amp; CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China  11 Beiyitiao, Zhongguancun Beijing 100190 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotu","family":"Ma","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety &amp; 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